Vascular endothelial cell growth factor (VEGF) is a novel angiogenic factor with mitogenic activity and apparent target specificity for vascular endothelial cells. This mitogen is synthesized by normal smooth muscle cells and by many malignantly transformed cells, which suggests that VEGF is involved in normal angiogenic processes and in tumor angiogenesis. The narrow target specificity of VEGF stands in marked contrast to the broad range of cell types stimulated by the endothelial cell mitogens acidic and basic fibroblast growth factors. We have shown that VEGF bound to two affinity classes of binding sites and could be cross-linked to three sites of different masses on human umbilical vein endothelial cells. In addition VEGF stimulated the specific tyrosine phosphorylation of at least one endothelial cell protein. In order to study the mechanism of action of VEGF in more detail than is currently possible, characterization of the receptors for VEGF is necessary. Thus, we propose to clone VEGF receptor cDNA from human umbilical vein endothelial cells. By analogy with other growth factor-receptor systems, the determination of VEGF receptor primary structure should reveal a wealth of information about VEGF-induced signaling and suggest directions for further research.